ATE254111T1 - PYRIMIDINE DERIVATIVES AS INTERLEUKIN INHIBITORS - Google Patents

PYRIMIDINE DERIVATIVES AS INTERLEUKIN INHIBITORS

Info

Publication number
ATE254111T1
ATE254111T1 AT95915448T AT95915448T ATE254111T1 AT E254111 T1 ATE254111 T1 AT E254111T1 AT 95915448 T AT95915448 T AT 95915448T AT 95915448 T AT95915448 T AT 95915448T AT E254111 T1 ATE254111 T1 AT E254111T1
Authority
AT
Austria
Prior art keywords
beta
compounds
pyrimidine derivatives
aspartic acid
protease activity
Prior art date
Application number
AT95915448T
Other languages
German (de)
Inventor
Roland E Dolle
Catherine P Prouty
Prasad V Chaturvedula
Stanley J Schmidt
Original Assignee
Vertex Pharma
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Vertex Pharma filed Critical Vertex Pharma
Application granted granted Critical
Publication of ATE254111T1 publication Critical patent/ATE254111T1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6509—Six-membered rings
    • C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Disclosed are compounds, compositions and methods for inhibiting interleukin-1 beta (1L- beta ) protease activity. The compounds, N-(pyrimidinyl)-aspartic acid alpha -substituted methyl ketones and aspartic acid aldehydes, have the formula (I) set out herein. These compounds are inhibitors of 1 beta -converting enzyme and as such are useful whenever such inhibition is desired. For example, they may be used as research tools in pharmacological, diagnostic and related studies and in the treatment of diseases in mammals in which IL- beta protease activity is implicated.
AT95915448T 1994-03-31 1995-03-29 PYRIMIDINE DERIVATIVES AS INTERLEUKIN INHIBITORS ATE254111T1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US22171294A 1994-03-31 1994-03-31
PCT/US1995/003909 WO1995026958A1 (en) 1994-03-31 1995-03-29 Pyrimidinyl derivatives as interleukin inhibitors

Publications (1)

Publication Number Publication Date
ATE254111T1 true ATE254111T1 (en) 2003-11-15

Family

ID=22829018

Family Applications (1)

Application Number Title Priority Date Filing Date
AT95915448T ATE254111T1 (en) 1994-03-31 1995-03-29 PYRIMIDINE DERIVATIVES AS INTERLEUKIN INHIBITORS

Country Status (18)

Country Link
US (3) US5670494A (en)
EP (1) EP0752987B1 (en)
JP (1) JP3703836B2 (en)
CN (2) CN1504462A (en)
AT (1) ATE254111T1 (en)
AU (1) AU703451B2 (en)
CA (1) CA2186511C (en)
DE (1) DE69532113T2 (en)
DK (1) DK0752987T3 (en)
ES (1) ES2210289T3 (en)
FI (1) FI112943B (en)
HK (1) HK1012623A1 (en)
HU (1) HU224731B1 (en)
MX (1) MX9604420A (en)
NO (1) NO308603B1 (en)
NZ (1) NZ283876A (en)
PT (1) PT752987E (en)
WO (1) WO1995026958A1 (en)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5874424A (en) * 1995-12-20 1999-02-23 Vertex Pharmaceuticals Incorporated Inhibitors of interleukin-1β converting enzyme
US6008217A (en) * 1995-12-20 1999-12-28 Vertex Pharmaceuticals Incorporated Inhibitors of interleukin-1β converting enzyme
US6204261B1 (en) * 1995-12-20 2001-03-20 Vertex Pharmaceuticals Incorporated Inhibitors of interleukin-1β Converting enzyme inhibitors
US5714484A (en) * 1993-12-08 1998-02-03 Prototek, Inc. α-(1,3-dicarbonylenol ether) methyl ketones as cysteine protease inhibitors
MX9604420A (en) 1994-03-31 1997-12-31 Sanofi Winthrop Inc Pyrimidinyl derivatives as interleukin inhibitors.
US5756466A (en) * 1994-06-17 1998-05-26 Vertex Pharmaceuticals, Inc. Inhibitors of interleukin-1β converting enzyme
US5716929A (en) * 1994-06-17 1998-02-10 Vertex Pharmaceuticals, Inc. Inhibitors of interleukin-1β converting enzyme
US6420522B1 (en) 1995-06-05 2002-07-16 Vertex Pharmaceuticals Incorporated Inhibitors of interleukin-1β converting enzyme
US5847135A (en) * 1994-06-17 1998-12-08 Vertex Pharmaceuticals, Incorporated Inhibitors of interleukin-1β converting enzyme
US6001814A (en) * 1994-11-21 1999-12-14 Cortech Inc. Serine protease inhibitors
WO1996018644A1 (en) * 1994-12-13 1996-06-20 Corvas International, Inc. Aromatic heterocyclic derivatives as enzyme inhibitors
US6011158A (en) * 1994-12-13 2000-01-04 Corvas International, Inc. Aromatic heterocyclic derivatives as enzyme inhibitors
AU5122196A (en) * 1995-03-31 1996-10-16 Takeda Chemical Industries Ltd. Cysteine protease inhibitor
CN1131210C (en) * 1995-04-27 2003-12-17 三菱制药株式会社 Heterocyclic amide compounds and medicinal use of the same
US5843904A (en) * 1995-12-20 1998-12-01 Vertex Pharmaceuticals, Inc. Inhibitors of interleukin-1βconverting enzyme
US6136834A (en) * 1995-12-27 2000-10-24 Ono Pharmaceutical Co., Ltd. Tetrazole compounds and pharmaceutical agents containing such derivative
US5919790A (en) * 1996-10-11 1999-07-06 Warner-Lambert Company Hydroxamate inhibitors of interleukin-1β converting enzyme
JP2001502330A (en) * 1996-10-11 2001-02-20 ワーナー―ランバート・コンパニー Sulfonamide-substituted aspartate interleukin-1β converting enzyme inhibitor
ES2188906T3 (en) 1996-10-11 2003-07-01 Warner Lambert Co INHIBITORS OF THE CONVERSION ENZYME OF INTERLEUCINE-1BETA BASED ON SULFONAMIDE.
AU1466399A (en) * 1998-01-20 1999-08-02 Basf Aktiengesellschaft N-(2-(5-benzyloxycarbonyl-amino-6-oxo-2-(4-fluorophenyl)-1,6 -dihydro-1-pyrimidinyl)aceto- xyl)-l-aspartic acid aldehyde as an (in vivo) inhibitor of interleukin-1beta converting enzyme (ice)
AU2901899A (en) 1998-03-09 1999-09-27 Vertex Pharmaceuticals Incorporated 1,2-diazepane derivatives as interleukin-1beta converting enzyme inhibitors
KR100928878B1 (en) 1998-03-19 2009-11-30 버텍스 파마슈티칼스 인코포레이티드 Inhibitors of caspases
WO2000032216A1 (en) * 1998-06-03 2000-06-08 Cortech Inc. Peptoid and nonpeptoid containing alpha-keto oxadiazoles as serine protease inhibitors
ES2527760T3 (en) * 1998-07-23 2015-01-29 Yeda Research And Development Co., Ltd. Treatment of Crohn's disease with copolymer 1 and polypeptides
WO2000005250A1 (en) 1998-07-23 2000-02-03 Yeda Research And Development Co., Ltd Treatment of autoimmune conditions with copolymer 1 and related copolymers and peptides
US6800287B2 (en) 1998-09-25 2004-10-05 Yeda Research And Development Co., Ltd. Copolymer 1 related polypeptides for use as molecular weight markers and for therapeutic use
US6972296B2 (en) 1999-05-07 2005-12-06 Encysive Pharmaceuticals Inc. Carboxylic acid derivatives that inhibit the binding of integrins to their receptors
US7022663B2 (en) * 2000-02-18 2006-04-04 Yeda Research And Development Co., Ltd. Oral, nasal and pulmonary dosage formulations of copolymer 1
EP2241328A1 (en) 2000-05-12 2010-10-20 Immunex Corporation Interleukin-1 inhibitors in the treatment of diseases
PE20011350A1 (en) 2000-05-19 2002-01-15 Vertex Pharma PROPHARMAC OF AN INHIBITOR OF INTERLEUKIN-1ß CONVERTER ENZYME (ICE)
US20020077278A1 (en) 2000-06-05 2002-06-20 Yong V. Wee Use of glatiramer acetate (copolymer 1) in the treatment of central nervous system disorders
WO2002076503A1 (en) * 2000-06-20 2002-10-03 Mayo Foundation For Medical Education And Research Treatment of central nervous system diseases by antibodies against glatiramer acetate
CA2416248A1 (en) * 2000-07-18 2002-01-24 Neurogen Corporation 5-substituted 2-aryl-4-pyrimidinones
ES2349033T3 (en) * 2001-12-04 2010-12-22 Teva Pharmaceutical Industries, Ltd. PROCEDURES FOR MEASURING THE ACTIVITY OF GLATIRAMER ACETATE.
US7410956B2 (en) * 2002-02-11 2008-08-12 Vertex Pharmaceuticals Incorporated Caspase inhibitor prodrugs
US7001899B2 (en) * 2002-06-10 2006-02-21 The Procter & Gamble Company Interleukin converting enzyme inhibitors
EP1553090A4 (en) * 2002-06-14 2006-07-05 Ajinomoto Kk Process for producing pyrimidine compound
PE20050159A1 (en) 2003-05-27 2005-04-19 Vertex Pharma DERIVATIVES OF 3- [2- (3-AMINO-2-OXO-2H-PYRIDIN-1-IL) -ACETILAMINO] -4-OXO-PENTANOICO AS CASPASE INHIBITORS
WO2005117846A2 (en) 2004-05-27 2005-12-15 Vertex Pharmaceuticals Incorporated Ice inhibitors for the treatment of autoinflammatory diseases
CN1980648A (en) * 2004-05-15 2007-06-13 沃泰克斯药物股份有限公司 Treating seizures using ICE inhibitors
CA2588713A1 (en) * 2004-11-24 2006-06-01 Vertex Pharmaceuticals Incorporated 3-[2-(3-acylamino-2-oxo-2h-pyridin-1-yl)-acetylamino]-4-oxo-pentanoic acid derivatives and their use as caspase inhibitors
JP2010535167A (en) * 2007-08-03 2010-11-18 サノフィ−アベンティス Caspase imaging probe
EP2262783A2 (en) * 2008-02-21 2010-12-22 Sanofi-Aventis Covalently binding imaging probes
US20140309172A1 (en) 2010-11-05 2014-10-16 Dagmar Ringe Ice inhibiting compounds and uses thereof
US9956260B1 (en) 2011-07-22 2018-05-01 The J. David Gladstone Institutes Treatment of HIV-1 infection and AIDS
EP2848696A1 (en) 2013-09-13 2015-03-18 Sanofi-Aventis Deutschland GmbH Caspase-1 imaging probes

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5441960A (en) * 1992-04-16 1995-08-15 Zeneca Limited 1-pyrimidinylacetamide human leukocyte elastate inhibitors
MX9604420A (en) * 1994-03-31 1997-12-31 Sanofi Winthrop Inc Pyrimidinyl derivatives as interleukin inhibitors.

Also Published As

Publication number Publication date
MX9604420A (en) 1997-12-31
AU703451B2 (en) 1999-03-25
FI963897A0 (en) 1996-09-27
HUT75715A (en) 1997-05-28
JPH09511249A (en) 1997-11-11
HU9602664D0 (en) 1996-11-28
HK1012623A1 (en) 1999-08-06
AU2232395A (en) 1995-10-23
DK0752987T3 (en) 2004-03-15
WO1995026958A1 (en) 1995-10-12
NO964058L (en) 1996-09-26
ES2210289T3 (en) 2004-07-01
EP0752987B1 (en) 2003-11-12
CA2186511C (en) 2009-02-10
CA2186511A1 (en) 1995-10-12
HU224731B1 (en) 2006-01-30
CN1118458C (en) 2003-08-20
CN1149292A (en) 1997-05-07
PT752987E (en) 2004-03-31
US20010003750A1 (en) 2001-06-14
US6162800A (en) 2000-12-19
EP0752987A1 (en) 1997-01-15
CN1504462A (en) 2004-06-16
NZ283876A (en) 2001-03-30
DE69532113D1 (en) 2003-12-18
US6407080B2 (en) 2002-06-18
NO308603B1 (en) 2000-10-02
NO964058D0 (en) 1996-09-26
EP0752987A4 (en) 1997-04-09
US5670494A (en) 1997-09-23
JP3703836B2 (en) 2005-10-05
FI112943B (en) 2004-02-13
FI963897A (en) 1996-09-27
DE69532113T2 (en) 2004-07-29

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